Acquired sensory neuronopathies (hereinafter abbreviated as “SNN”) are a specific subgroup of peripheral nervous system diseases characterized by primary involvement of sensory neurons in the dorsal root ganglia (Kuntzer at al., Muscle Nerve, 2004; 30:255-268; Sghirlanzoni at al., Lancet Neurol., 2005; 4:349-361). SNNs encompass different paraneoplastic, viral, dysimmune, toxic, and idiopathic disorders.
Lesions in the dorsal root ganglia have been demonstrated pathologically in paraneoplastic SNN (Graus at al., Neurology, 1990; 40:219-222; Dalmau J et al., Neurology 1991; 41:1757-1764; Wanschitz at al. Neurology, 1997; 49:1156-1159.), HIV infection (Scaravili et al., Acta. Neuropathol. (Berl), 1992; 84:163-170; Esiri at al., J. Neurol. Sci., 1993; 114:178-187), Sjögren's syndrome (Mori et al., Brain, 2005; 128:2518-2534; Griffin et al., Ann. Neurol., 1990; 27304-315), and unclassified connective diseases, but also in some idiopathic cases (Okajima et al. Neurology, 1983; 33:1061-1064; Sobue et al., Neurology, 1988; 38:463-467; Hainfellner et al., Ann. Neurol., 1996; 39:543-547; Kurokawa at al., J. Neurol. Neurosurg. Psychiatry, 1998; 65:278-279; Colli at al., Surg. Neurol., 2008; 69:266-273).
Recently, a set of clinical criteria that help to differentiate SNN from other sensory neuropathies has been published, but these criteria do not allow SNN to be distinguished according to their etiologies (Camdessanche a al., Brain, 2009; 132:1723-1733).
In particular, among SNN without an overt associated autoimmune context, it is at present not possible to distinguish on clinical grounds autoimmune SNN from non autoimmune idiopathic forms.
In addition, as these criteria were deliberately conceived to be stringent, they probably miss incomplete forms of SNN. As biopsy of dorsal root ganglia is not feasible as a routine investigation and because of the absence of methods that allow easy and non-traumatic exploration of dorsal root ganglia, there is a need for biological tools that may help to distinguish SNN from the far more numerous other form of sensory neuropathies.
Auto-antibodies reactive with sensory neuron antigens, mainly auto-antibodies called anti-Hu antibodies, have been identified in paraneoplastic SNN only (Camdessanche et al., Brain, 2009; 132:1723-1733; Graus et al., J. Neurol. Neurosurg. Psychiatry, 2004; 75:1135-1140; Camdessanche et al., Brain, 2002; 125:166-175; U.S. Pat. No. 6,193,948). A handful of studies using the serum of occasional patients with SNN and Sjögren's syndrome or idiopathic SNN tested on various substrates gave inconclusive results (Murata et al., Neuroreport., 2005; 16:677-681; Eystathloy et al., J. Mol. Med., 2003; 81:811-618; Dalakas M C, Ann. Neurol., 1986; 19:545-564; Nemni et al., Ann. Neurol., 1993; 34:848-854; van Dijk et al., J. Neuroimmunol., 1997; 74:165-172; Muloh et al., Arch. Neurol., 2005; 62:1612-1615).
Differentiating SNN from other sensory neuropathies is important owing to the possibility of detecting disorders that may benefit from specific investigations and treatments.
Further, knowing whether an autoimmune process is involved in idiopathic cases or a subgroup of these is important, since it may lead to the development of immunomodulatory treatments and help to distinguish these cases from other sensory neuropathies.
The inventors have now shown that serum immunoreactivity toward fibroblast growth factor receptor (FGFR) family and related proteins, as well as toward proteins that belong to growth factor receptor-bound protein family, identify a subgroup of patients with SNN in which a dysimmune process is involved, suggesting that this subgroup of patients may be treated with immunosuppressants and/or immunomodulators.